Ojanen Sami P, Hyytiä Petri, Kiianmaa Kalervo
Department of Mental Health and Alcohol Research, National Public Health Institute, Helsinki, Finland.
Alcohol Clin Exp Res. 2006 Apr;30(4):621-9. doi: 10.1111/j.1530-0277.2006.00072.x.
Alcohol-preferring alko alcohol (AA) rats are more susceptible to morphine-induced behavioral and neurochemical sensitization than alcohol nonpreferring alko nonalcohol (ANA) rats. Alko alcohol rats sensitized to morphine, however, do not show enhanced acquisition of ethanol drinking. The purpose of the present study was to clarify further interactions between morphine-induced behavioral sensitization and voluntary ethanol drinking in the AA rats.
Alko alcohol rats drinking ethanol in a limited 6-hour access paradigm were sensitized to morphine with repeated injections of morphine (5-15 mg/kg). Injection days alternated with days of ethanol access. Controls had access only to water and/or were given injections of saline. After a 5-day washout period from ethanol and morphine, the rats were challenged with morphine or saline and subsequent ethanol drinking or locomotor activity was recorded.
Ethanol intake was suppressed during the repeated treatment with morphine, and the morphine-treated rats did not differ in ethanol intake from the controls when given access to ethanol after the washout. Intake of ethanol was, however, increased when the rats were challenged with morphine [1 or 10 mg/kg, subcutaneously (s.c.)], while in the controls an increase in ethanol intake was seen only after 1 mg/kg morphine. Sensitization to the locomotor stimulating effects of morphine was revealed in the morphine-treated rats after a challenge with morphine (3 or 10 mg/kg, s.c.). The controls that had been drinking ethanol also showed a sensitized response after morphine (3 mg/kg).
Ethanol did not interfere with the development of sensitization to morphine. Furthermore, the neuroadaptations induced by repeated exposure to ethanol were sufficient to cause behavioral cross-sensitization to morphine. Sensitization to the behavioral effects of morphine alone, however, neither enhances the reinforcing properties of voluntarily consumed ethanol nor contributes to increase in its intake. The increase in ethanol intake found after an acute dose of morphine was augmented in rats withdrawn from repeated treatment with morphine. The data suggest that the neuronal mechanisms underlying behavioral sensitization to morphine probably are distinct from those mediating reinforcement from ethanol and that the morphine-induced neuroadaptations contribute to the enhancement of increase in ethanol intake by morphine.
嗜酒的阿尔科酒精（AA）大鼠比不嗜酒的阿尔科非酒精（ANA）大鼠更容易对吗啡诱导的行为和神经化学敏化产生反应。然而，对吗啡敏感的阿尔科酒精大鼠并未表现出乙醇摄取习得的增强。本研究的目的是进一步阐明AA大鼠中吗啡诱导的行为敏化与自愿乙醇摄取之间的相互作用。
在有限的6小时摄取模式下饮用乙醇的阿尔科酒精大鼠通过重复注射吗啡（5 - 15毫克/千克）对吗啡产生敏化。注射日与乙醇摄取日交替。对照组仅能获取水和/或接受盐水注射。在从乙醇和吗啡中洗脱5天后，用吗啡或盐水对大鼠进行激发，随后记录乙醇摄取或运动活性。
在吗啡重复治疗期间乙醇摄取受到抑制，在洗脱后给予乙醇时，接受吗啡治疗的大鼠与对照组在乙醇摄取方面没有差异。然而，当大鼠用吗啡[1或10毫克/千克，皮下注射（s.c.）]激发时，乙醇摄取增加，而在对照组中，仅在1毫克/千克吗啡后才观察到乙醇摄取增加。在用吗啡（3或10毫克/千克，s.c.）激发后，接受吗啡治疗的大鼠表现出对吗啡运动刺激作用的敏化。饮用乙醇的对照组在给予吗啡（3毫克/千克）后也表现出敏化反应。
乙醇并未干扰对吗啡敏化的发展。此外，反复接触乙醇诱导的神经适应性足以导致对吗啡的行为交叉敏化。然而，仅对吗啡行为效应的敏化既不会增强自愿摄取乙醇的强化特性，也不会导致其摄取增加。在从吗啡重复治疗中撤药的大鼠中，急性剂量吗啡后发现的乙醇摄取增加更为明显。数据表明，对吗啡行为敏化的潜在神经机制可能与介导乙醇强化作用的机制不同，并且吗啡诱导的神经适应性有助于增强吗啡引起的乙醇摄取增加。
